Tamsulosin hydrochloride is a selective α1 adrenergic antagonist that has been shown to improve symptoms and urinary flow rate in patients with benign prostatic hyperplasia (BPH).
Commercially marketed product is a hydrochloride salt of the (R) enantiomer of tamsulosin.
EP034432 and U.S. Pat. No. 4,373,106 disclose the preparation of racemic tamsulosin by two processes:
1) “Process A” comprises the condensation of the ketone of formula A with the amine of formula B followed by reduction of the intermediate Schiff base formed.
2) “Process B” describes a process that goes through a hydroxyl and a chloro-analogue intermediates followed by reduction of the chloro analogue intermediate, according to the following sequence:

The above processes have the disadvantage that they need further resolution of the racemic product to obtain the desired more active R(−) tamsulosin. Processes for this difficult resolution of the racemic mixture are described, for example, in Japanese Patent Application No. JP-56-110665, in WO03/037850 and in WO2004/006829.
U.S. Pat. No. 4,731,478, U.S. Pat. No. 4,761,500 and U.S. Pat. No. 5,447,958 in addition to the two processes above mentioned for the preparation of racemic tamsulosin disclose a process for the preparation of both optically pure enantiomers of tamsulosin.
The process comprises the preparation of any of the two optically pure 5-(2-amino-propyl)-2-methoxy-benzenesulphonamide enantiomers followed by reaction with 2-(o-ethoxy-phenoxy)ethyl bromide compound of formula D to form the corresponding (R) and (S) tamsulosin. The process for the preparation of the R(−) tamsulosin isomer is illustrated in the following scheme:

This process has the disadvantage that the starting compound (2R)-2-(4-methoxy-phenyl)-1-methyl-ethylamine is a known hallucinogenic substance, handling of which is undesirable.
EP257787 and its divisional EP380144 disclose:
1) An alternative process for the preparation, among others, of the pure optically amine of formula C
according to the following scheme:
2) The process for the preparation of R(−) tamsulosin via coupling pure amine C with the bromide D.

This process requires a chromatographic purification in a silica gel column.
WO 02/068382 discloses the preparation of R(−) tamsulosin via reduction of the related intermediate E of the optically pure amine C, according to the following scheme.

We have now devised an improved process for the preparation of tamsulosin, which process overcomes or substantially minimises the problems associated with the prior art processes.